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Hypothetical Pathway for Formation of Cholesterol Microcrystals Initiating the Atherosclerotic Process. Cell Biochem Biophys 2020 Sep;78(3):241-247

Date

07/01/2020

Pubmed ID

32602057

Pubmed Central ID

PMC7403164

DOI

10.1007/s12013-020-00925-2

Abstract

Major factors leading to the development of atherosclerosis are a high cholesterol (Chol) level in the blood and oxidative stress. Both promote the formation of Chol microcrystals in blood vessel walls. Deposition of Chol microcrystals in arterial intima causes inflammation, which initiates and accompanies the atherosclerotic process in all its phases. One of the possible sources of Chol in the blood vessel walls is oxidized low-density lipoproteins-this atherosclerotic plaque formation pathway has already been described in the literature. Here, we hypothesize that initiation of the atherosclerotic process may involve Chol domains in the plasma membranes of arterial cells. Increased Chol content and the presence of polyunsaturated phospholipids in these membranes together with oxidative stress (phospholipid peroxidation) may lead to the formation of pure Chol bilayer domains that, with further peroxidation and increased Chol content, may collapse in the form of Chol seed crystals. Independent of their origin, Chol microcrystals activate inflammasomes, thereby stimulate immune responses, and initiate inflammation that may lead to the development of atherosclerosis. This new, hypothetical pathway has not yet been investigated in depth; however, data from the literature and our own results support its feasibility.

Author List

Subczynski WK, Pasenkiewicz-Gierula M

Author

Witold K. Subczynski PhD Professor in the Biophysics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Atherosclerosis
Cell Membrane
Cholesterol
Crystallization
Humans
Hypercholesterolemia
Inflammation
Lipid Bilayers
Lipoproteins, LDL
Models, Biological
Oxidative Stress
Phospholipids
Plaque, Atherosclerotic